Minimization of Ischemic Cholangiopathy in Donation After Cardiac Death Liver Transplantation: Is It Thrombolytic Therapy or Warm Ischemic Time Stringency and Donor Bile Duct Flush?

To the Editor: Donation after cardiac death (DCD) liver transplantation (LT) is the fastest expanding donor pool. Despite its promise, initial DCD experience showed discouraging outcomes (1Merion RM Pelletier SJ Goodrich N Englesbe MJ Delmonico FL Donation after cardiac death as a strategy to increase deceased donor liver availability.Ann Surg. 2006; 244: 555-562PubMed Google Scholar). Cumulative experience from aggressive LT centers re-ignited the interest in DCD LT (2Muiesan P Girlanda R Jassem W et al.Single-center experience with liver transplantation from controlled NHBDs: A viable source of grafts.Ann Surg. 2005; 242: 732-738Crossref PubMed Scopus (153) Google Scholar), culminating in outstanding outcomes, comparable to that of donation after brain death (DBD) (3Bohorquez H Seal JB Cohen AJ et al.Safety and outcomes in 100 consecutive donation after circulatory death liver transplants using a protocol that includes thrombolytic therapy.Am J Transplant. 2017; 17: 2155-2164Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar). Ischemic cholangiopathy (IC) is the Achilles heel of DCD LT. It is attributed to microthrombi formation in the peribiliary vascular plexus during the donor terminal events, resulting in biliary injury (4Hashimoto K Eghtesad B Gunasekaran G et al.Use of tissue plasminogen activator in liver transplantation from donation after cardiac death donors.Am J Transplant. 2010; 1: 2665-2672Abstract Full Text Full Text PDF Scopus (108) Google Scholar). Based on this hypothesis, the University of Toronto and Oschner Clinic demonstrated significantly decreased IC rates after tissue plasminogen activator (tPA) administration (5Seal JB Bohorquez H Reichman T et al.Thrombolytic protocol minimizes ischemic-type biliary complications in liver transplantation from donation after circulatory death donors.Liver Transpl. 2015; 21: 321-328Crossref PubMed Scopus (70) Google Scholar). The Oschner DCD protocol also includes fast organ recovery, with short waiting and warm ischemia times, copious common bile duct flushing, retrograde hepatic vein flushing, verapamil and heparin administration on the recipient side, combined with expeditious implantation. The above modifications have resulted in minimization of IC incidence to 3% and graft survival comparable to that of DBD. In the UK DCD practice, withdrawal of life support never takes place in the operating room. No heparin can be administered to the donor before death. Stand-off is fixed at 5 minutes and commences with asystole, not on pulseless electrical activity or ventricular fibrillation, a common United States practice. At King’s DCD protocol, the functional donor warm ischemia time (fWIT) is defined as the time from when oxygen saturation is <70% and/or systolic blood pressure is <50 mmHg to aortic cannulation. As a result, asystole-to-cross-clamp time may be significantly longer in the United Kingdom. If the King’s fWIT is over 30 min, the liver is usually not transplanted. In the period 2004–2015, 318 DCD LTs (adults and pediatrics) have been performed at King’s College Hospital (15% of 2115 LTs), with a persistently low incidence of IC (3%) and DCD DBD graft survival equivalence. Other key and consistent aspects in the King’s College Hospital DCD practice from 2001 are the following:1superfast procurement with emphasis on initial organ decongestion, dual in situ aortic and portal perfusion, flushing of the biliary tree in situ, rapid hepatectomy (<30 min), and a liver packed for transportation within an hour of donor asystole,2fWIT stringency in terms of definition and DCD use.3prudence in balancing the DCD recipient risk, and4implantation without technical complications. The Oschner Clinic and King’s cohorts report a similar IC incidence (3%) and a DCD graft survival equal to DBD. Both programs practice expeditious protocolized procurement with emphasis on early venous decompression, organ cooling and copious flushing of the biliary system. Additionally, in the late Oschner DCD group there is increasing use of DCD in hepatocellular cancer, lower Mayo End-Stage Liver Disease, and adherence to shorter warm ischemic times (based on systolic <80 mmHg or saturations of 80%). It is therefore worth questioning whether it is the “lege artis” procurement technique, expeditious donor biliary flush, donor–recipient matching, and fWIT stringency shared by both institutions, rather than the premortem donor heparin administration and postportal reperfusion tPA, that need to be highlighted for the exceedingly low IC rates and excellent DCD graft survival. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.